Research Interests
Tumor cell biology and drug resistance

My laboratory has been focusing on understanding of the molecular basis of tumorigenesis and tumor drug resistance.
Post-translational modifications play a pivotal role in regulating cellular functions because vast majority of critical proteins, such as transcription factors and nuclear receptors, are subject to such modifications. Small ubiquitin-related modifier (SUMO) conjugations or sumoylation has been recently identified and implicated in regulating a variety of cellular pathways. Like ubiquitination, sumoylation is a multiple step process, involving maturation, activation, conjugation and de-conjugation. As an E2 conjugating enzyme, Ubc9 is essential for sumoylation. Although it is well demonstrated that alterations of ubiquitination pathways can lead to development of cancer, the role for sumoylation in this aspect is unclear. Our recent studies have indicated that Ubc9 plays a role in tumorigenesis. Our long-term goals are to better understand the basis for Ubc9-mediated tumorigenesis and to develop Ubc9-based therapeutic agents for cancer treatment.
A second project is on microRNAs. MicroRNAs are a class of naturally occurring small non-coding RNAs that control gene expression through post-transcriptional regulation. To date, over 400 human microRNAs have been reported. Of interest, aberrant expression of microRNAs has been associated with human disorders, in particular cancer. While some microRNAs function as tumor suppressor, others function as oncogenes. We have recently shown that mir-21 is overexpressed in several types of tumors compared to the matched normal tissues and that more importantly, suppression of mir-21 by a mir-21 inhibitor substantially reduces tumor growth in a xenograft carcinoma mouse model, suggesting that mir-21 is an oncogenic microRNA. we believe that microRNAs play a critical role in cancer initiation, progression and metastasis, and thus, they, in particular oncogenic microRNAs such as mir-21, are novel therapeutic targets. Therefore, characterization of microRNA pathways leading to tumorigenesis will provide new insight into molecular mechanisms underlying microRNA-mediated gene regulation. As a result, this knowledge will aid in developing microRNA-based therapeutic agents for cancer therapy.

Selected Publications

1. Leavenworth JW, Ma X, Mo YY, Pauza ME. SUMO conjugation contributes to immune deviation in nonobese diabetic mice by suppressing c-Maf transactivation of IL-4.J Immunol. 2009 Jul 15;183(2):1110-9. Epub 2009 Jun 24. PubMed PMID: 19553542.
2. Jiang Q, Feng M, Mo YY. Systematic validation of predicted microRNAs forcyclin D1. BMC Cancer. 2009 Jun 18;9(1):194. [Epub ahead of print] PubMed PMID:19538740.
3. Peng S, Wu H, Mo YY, Watabe K, Pauza ME. c-Maf increases apoptosis inperipheral CD8 cells by transactivating Caspase 6. Immunology. 2009Jun;127(2):267-78. PubMed PMID: 19476513; PubMed Central PMCID: PMC2691792.
4. Huang TH, Wu F, Loeb GB, Hsu R, Heidersbach A, Brincat A, Horiuchi D, Lebbink RJ, Mo YY, Goga A, McManus MT. Up-regulation of miR-21 by HER2/neu SignalingPromotes Cell Invasion. J Biol Chem. 2009 Jul 3;284(27):18515-24. Epub 2009 May6. PubMed PMID: 19419954; PubMed Central PMCID: PMC2709372.
5. Sachdeva M, Mo YY. p53 and c-myc: how does the cell balance "yin" and "yang"? Cell Cycle. 2009 May 1;8(9):1303. Epub 2009 May 3. PubMed PMID: 19342882.
6. Wu H, Zhu S, Mo YY. Suppression of cell growth and invasion by miR-205 inbreast cancer. Cell Res. 2009 Apr;19(4):439-48. PubMed PMID: 19238171; PubMedCentral PMCID: PMC2664859.
7. Wu F, Zhu S, Ding Y, Beck WT, Mo YY. MicroRNA-mediated regulation of Ubc9expression in cancer cells. Clin Cancer Res. 2009 Mar 1;15(5):1550-7. Epub 2009 Feb 17. PubMed PMID: 19223510.
8. Sachdeva M, Zhu S, Wu F, Wu H, Walia V, Kumar S, Elble R, Watabe K, Mo YY. p53represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl AcadSci U S A. 2009 Mar 3;106(9):3207-12. Epub 2009 Feb 6. PubMed PMID: 19202062;PubMed Central PMCID: PMC2651330.
9. Furuta E, Pai SK, Zhan R, Bandyopadhyay S, Watabe M, Mo YY, Hirota S, HosobeS, Tsukada T, Miura K, Kamada S, Saito K, Iiizumi M, Liu W, Ericsson J, Watabe K.Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt andsterol regulatory element binding protein-1. Cancer Res. 2008 Feb15;68(4):1003-11. PubMed PMID: 18281474.
10. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumorsuppressor genes in invasion and metastasis. Cell Res. 2008 Mar;18(3):350-9.PubMed PMID: 18270520.
11. Wu F, Chiocca S, Beck WT, Mo YY. Gam1-associated alterations of drugresponsiveness through activation of apoptosis. Mol Cancer Ther. 2007Jun;6(6):1823-30. PubMed PMID: 17575111.
12. Wu F, Stutzman A, Mo YY. Notch signaling and its role in breast cancer. FrontBiosci. 2007 May 1;12:4370-83. Review. PubMed PMID: 17485381.
13. Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor genetropomyosin 1 (TPM1). J Biol Chem. 2007 May 11;282(19):14328-36. Epub 2007 Mar15. PubMed PMID: 17363372.
14. Wu F, Mo YY. Ubiquitin-like protein modifications in prostate and breastcancer. Front Biosci. 2007 Jan 1;12:700-11. Review. PubMed PMID: 17127330.
15. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth.Oncogene. 2007 Apr 26;26(19):2799-803. Epub 2006 Oct 30. PubMed PMID: 17072344.